Accumulating evidence has shown that the tumor microenvironment is critically important for the initiation and progression of cancer. The tumor microenvironment consists of several components including tumor cells, myofibroblasts, stellate cells, peritumor nerve cells, endothelial cells, immune cells and endocrine cells, as well as extracellular components such as the extracellular matrix. While it is recognized that these components are mediators of tumorigenesis, the complex interplay of these components is poorly understood. Research efforts to investigate the mechanisms of tumor microenvironment interactions in the primary tumor site and organs that are common sites of metastatic lesions are critically needed in order to identify potential targets for improved cancer treatment, as well as risk management and prevention. Hence, we believe that there is a clear need for new programs to train individuals at the graduate as well as the postgraduate levels to understand and efficiently investigate the complex processes that contribute to the conversion of normal stromal cells to an active tumor microenvironment that leads to tumor progression and metastasis. This proposal requests funding to support is 8 trainees (2 predoctoral, 6 postdoctoral) each year for 5 years The program objective is to provide integrated training to individuals who will conduct critically needed research investigating the molecular and cellular anomalies of tumor microenvironment components that result in tumor initiation, progression, metastasis, and relapse. The program is based on the idea that major progress, of clinical relevance, in the area of stromal and epithelial dysfunction of cancer formation will be enhanced by a concerted effort of investigators who have had substantial mentoring and experience in the fields of cell biology, vascular cell biology, extracellular matrix biology, cancer genetics, immunology, and clinical cancer research. The Tumor Microenvironment/Angiogenesis (TMA) Training Program involves 25 full faculty members, all of whom have extramurally supported programs and expertise in TMA-related areas. Dr. Mukhopadhyay will serve as director of the program. He is an experienced mentor and training program leader. He will be assisted by Dr. Mark McNiven, who is known world-wide for his expertise in cell biology and he has an outstanding training record. RELEVANCE: Despite the tremendous advancements in the diagnosis and treatment of cancer, we are far from achieving our optimal goal to "eradicate cancer." This training program will program will provide the next generation of cancer researchers with an integrated set of skills needed to understand the complex interactions of tumor cells and the cells surrounding them. This knowledge will be used to improve cancer prevention and treatment methods.